For years there have been warnings that advances in science could make it possible to cook up killer diseases in laboratories and unleash them on the world.

This week came news that scientists at the University of Alberta have put together from scratch a relative of the smallpox virus — and a reminder that the threat of deadly viruses created by humans is more than theoretical.

The smallpox virus, which triggered brutal disease for centuries, was declared eradicated in 1980 after a successful global effort to end its reign of terror. But some scientists fear that it could be revived through what’s known as synthetic biology — the ability to make a virus by putting together by the recipe outlined in its genetic code.

The horsepox virus the Canadian team created is not a threat to human health — or even the health of horses — should it ever escape from a lab. And it’s not the first virus created by putting pieces of DNA together in the right sequence.

Still, the news that a team headed by David Evans, a professor of medical microbiology and immunology, had accomplished this feat — at a relatively low cost of about $100,000 plus labor — was a bit of a wakeup call. The news was first reported Thursday in Science Magazine.

“This is an example of what modern technologies can do,” noted Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

The warnings about the implications of synthetic biology have echoed since Eckard Wimmer of the State University of New York at Stony Brook reported in 2002 that he and his team had made a poliovirus from scratch.

Polioviruses are small in comparison with poxviruses, and a far less complex task. But scientists watching this field feared it was only a matter of time before the obstacles to creating other viruses were surmounted.

Evans, who is a member of a World Health Organization advisory committee that reviews applications to do smallpox-related research, said he had warned the committee the science was there.

“Really, nobody in the field is surprised about that and we have been telling WHO that for years now,” he told STAT. “This technology is quite possible. And my sense is that we need to just accept that and move on.”

Evans wanted to prove the point. But he also had a bigger goal in mind. He is trying to develop cancer vaccines and wants to use a vaccinia virus — another relative of smallpox, often used in research — as a way to introduce cancer fighters to the immune system.

Learning how to make vaccinia viruses synthetically would speed this work.

Meanwhile, a pharmaceutical company named Tonix was interested in making a newer, better smallpox vaccine, using the horsepox virus as its delivery mechanism. Evans and his team agreed to make horsepox — which seems to have disappeared in nature — for the company. Tonix funded the research.

Evans, who is vice dean of research at the University of Alberta, sought and received approval from the university to do the work.

Had he been in the United States, though, it is not clear if he could have performed this work. The proposal would have certainly gone through more approval processes, Fauci said, adding he did not know if the work would have received a green light.

Those levels of approvals are the result of a protracted and at times heated debate in the U.S. about research that can be considered to pose security threats. Generally referred to as DURC — dual use research of concern — this is otherwise valid research that could be used by rogue agents to weaponize pathogens.

The debate was triggered when, in 2011, a Dutch scientist using U.S. government funding manipulated H7N9 bird flu viruses until they developed the ability to spread readily among ferrets. Ferrets are a stand-in for humans in flu research because viruses that can infect them can infect people.

Marc Lipsitch, a professor of epidemiology at Harvard University, was a vocal critic of the flu research and has been active in the debate since over restricting work that could be used for nefarious purposes.

Asked about Evans’s work, he expressed concern not so much about the work itself but about the fact the world now knows about it.

“Demonstrating this can be done — and then writing newspaper articles about it and Science magazine articles — will get the attention of people who might want to use it for the wrong reasons and they might have never known about that,” Lipsitch said.

The horsepox work hasn’t yet been published. In fact, it has been turned down by two journals so far. And Evans admits he’s struggling with how much detail to include in the manuscript when he next submits it.

“I don’t want to put in detailed instructions on how to do this. If you’re knowledgeable in the field, you’ll know enough to replicate it. And if you’re not knowledgeable in the field, you probably shouldn’t be doing it anyway, right?” he noted.

Lipsitch found Evans’s attitude reassuring, but was perhaps less sanguine about the fact that this research shows that as complicated science becomes easier to do, government control over it may lessen.

The rules the National Institutes of Health have put in place relate to work that is done with its funding. But Evans did the work outside the U.S. and with private money.

“As potentially dangerous work gets cheaper and easier, it becomes harder to control for all sorts of reasons — including the fact that the legal reach of government is greater for things that they finance than for things they don’t finance,” Lipsitch said.

Helen Branswell
ScientificAmerican

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